Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
J Neurophysiol. 2010 Dec;104(6):3334-44. doi: 10.1152/jn.00330.2010. Epub 2010 Sep 29.
DEG/ENaC channels have been broadly implicated in mechanosensory transduction, yet many questions remain about how these proteins contribute to complexes that sense mechanical stimuli. In C. elegans, two DEG/ENaC channel subunits are thought to contribute to a gentle touch transduction complex: MEC-4, which is essential for gentle touch sensation, and MEC-10, whose importance is less well defined. By characterizing a mec-10 deletion mutant, we have found that MEC-10 is important, but not essential, for gentle touch responses in the body touch neurons ALM, PLM, and PVM. Surprisingly, the requirement for MEC-10 in ALM and PLM is spatially asymmetric; mec-10 animals show significant behavioral and physiological responses to stimulation at the distal end of touch neuron dendrites, but respond poorly to stimuli applied near the neuronal cell body. The subcellular distribution of a rescuing MEC-10::GFP translational fusion was found to be restricted to the neuronal cell body and proximal dendrite, consistent with the hypothesis that MEC-10 protein is asymmetrically distributed within the touch neuron process. These results suggest that MEC-10 may contribute to only a subset of gentle touch mechanosensory complexes found preferentially at the proximal dendrite.
DEG/ENaC 通道广泛参与机械感觉转导,但这些蛋白质如何参与感知机械刺激的复合物仍有许多问题。在秀丽隐杆线虫中,两种 DEG/ENaC 通道亚基被认为有助于产生柔和触感转导复合物:MEC-4,它是柔和触感所必需的,而 MEC-10 的重要性则不太明确。通过对 mec-10 缺失突变体进行特征描述,我们发现 MEC-10 对体壁触摸神经元 ALM、PLM 和 PVM 的柔和触感反应很重要,但不是必需的。令人惊讶的是,MEC-10 在 ALM 和 PLM 中的需求具有空间不对称性;mec-10 动物对触摸神经元树突远端的刺激表现出显著的行为和生理反应,但对靠近神经元细胞体的刺激反应不佳。发现拯救 MEC-10::GFP 翻译融合物的亚细胞分布仅限于神经元细胞体和近端树突,这与 MEC-10 蛋白在触摸神经元过程中呈不对称分布的假设一致。这些结果表明,MEC-10 可能仅有助于在近端树突处优先发现的一部分柔和触感机械感觉复合物。